Bone has remarkable healing properties, but in more complicated conditions where the bone deficiency is greater than 2-3 times its diameter, the process of healing delays or fails. Trauma, bone tumor resections, and congenital deformities are the primary causes of long bone deficiency. As a result, grafting procedures are warranted to facilitate repair and regeneration to restore tissue function.
Bone grafting has become the second most common transplantation procedure, with approximately 2.2 million surgeries performed annually worldwide. Treatment traditionally employs transplanting tissue from one site to another, either in the same patient (autograft) or from a donor (allograft). While these opportunities can be life-saving for patients, the processes to obtain cadaveric graft material pose major risk and difficulties. Harvesting allografts introduce immunological concerns and pose risk of infection and rejection by patients' immune systems. Additionally, harvesting autografts is often costly, painful, and limited by donor site anatomical constraints.
There is a growing need for scaffolds as alternatives for bone graft material to address current shortages in musculoskeletal donor tissue, especially if there is massive segmental bone loss. Tissue-engineered scaffolds have been utilized to enhance the healing response of critically sized bone defects while addressing the drawbacks regarding “gold standard” autograft and allograft use, but overall provide insufficient mechanical support and do not mimic native bone tissue behavior. Improvement to bone grafting procedures with respect to biologically active scaffolds still remains a challenge and there are still no well-approved treatment modalities that satisfy all the requirements to achieve successful and secured healing.
Studies have reported post-operative infection rates as high as 26.3% for allografts and 12.4% for autografts, resulting in surgical revision rates of 47% for allografts and 17% for autografts. Deep infections in bone grafting procedures, such as in limb reconstructions, are a devastating complication and economic burden to both patients and the healthcare system. In tibial fractures alone, the annual incremental medical cost associated with fracture nonunion was $20,364 compared to patients who healed normally.
Alternatively, tissue-engineered biological scaffolds have been utilized as bone graft substitutes to facilitate bridging bone defects to restore tissue function while addressing the disadvantages of traditional grafting methods. However, improving bone grafting procedures with respect to biologically active scaffolds still remains a challenge as traditional fabrication methods are highly complex, involving several steps, and inhibit the ability to control the internal architecture, thereby producing isotropic material with pore sizes that are not always interconnected and do not allow for ample nutrient flow to sustain long term tissue vascularization. Interconnected networks with a porosity of at least 300 μm for bone are required for nutrient exchange and cell mitigation to promote bone regeneration and new tissue growth.
Immunological issues from allografts and local trauma from autograft bone harvesting may be reduced if biologically active, mechanically stable scaffolds are employed. The use of the scaffold of the present invention as alternative bone graft material will provide a better environment for graft incorporation as compared to current traditional methods, as supported by experimental validation, thereby leading to reduced procedure duration, improved bone fusion rates and improved clinical outcomes with respect to patients' return to activity scores.